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Effects of herbimycin A and its derivatives on growth and differentiation of Ph1-positive acute lymphoid leukemia cell lines.
Leuk Res 1994; 18(3):221-8LR

Abstract

The molecular basis of the Philadelphia chromosome (Ph1) is a structurally altered c-abl (bcr/abl) gene which encodes an abnormally large protein with protein tyrosine kinase activity. Herbimycin A, an inhibitor of tyrosine kinase, preferentially inhibited the growth of Ph1-positive acute lymphoid leukemia (ALL) cell lines, as well as Ph1-positive chronic myeloid leukemia (CML) cell lines. Although noncytotoxic concentrations of herbimycin A induced erythroid differentiation of two CML-derived cell lines, K562 and KU812, in a previous study, the differentiation-inducing effect of herbimycin A on Ph1-positive ALL cell lines was less strong. Herbimycin A enhanced some differentiation-associated properties of one Ph1-positive ALL cell line, L2, but the effect of herbimycin A on the other Ph1-positive ALL cell lines was cytotoxic rather than cytostatic (differentiation-inducing). Several derivatives of herbimycin A were synthesized and their effects on the cell proliferation of Ph1-positive CML and ALL cell lines were examined. The sensitivities of the Ph1-positive cell lines to herbimycin A derivatives were different from the data on the rat kidney cell line infected with Rous sarcoma virus (v-src) derived from a previous study, suggesting bcr/abl kinase may differ in sensitivity from other tyrosine kinases. Moreover, the sensitivities of the ALL cell lines were not the same as those of the CML cell lines. These results suggest that a specific inhibitor of bcr/abl kinase could be an effective antileukemic agent against Ph1-positive CML or ALL.

Authors+Show Affiliations

Department of Chemotherapy, Saitama Cancer Center Research Institute, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

8139288

Citation

Sato, S, et al. "Effects of Herbimycin a and Its Derivatives On Growth and Differentiation of Ph1-positive Acute Lymphoid Leukemia Cell Lines." Leukemia Research, vol. 18, no. 3, 1994, pp. 221-8.
Sato S, Honma Y, Hozumi M, et al. Effects of herbimycin A and its derivatives on growth and differentiation of Ph1-positive acute lymphoid leukemia cell lines. Leuk Res. 1994;18(3):221-8.
Sato, S., Honma, Y., Hozumi, M., Hayashi, Y., Matsuo, Y., Shibata, K., ... Tsuruoka, N. (1994). Effects of herbimycin A and its derivatives on growth and differentiation of Ph1-positive acute lymphoid leukemia cell lines. Leukemia Research, 18(3), pp. 221-8.
Sato S, et al. Effects of Herbimycin a and Its Derivatives On Growth and Differentiation of Ph1-positive Acute Lymphoid Leukemia Cell Lines. Leuk Res. 1994;18(3):221-8. PubMed PMID: 8139288.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of herbimycin A and its derivatives on growth and differentiation of Ph1-positive acute lymphoid leukemia cell lines. AU - Sato,S, AU - Honma,Y, AU - Hozumi,M, AU - Hayashi,Y, AU - Matsuo,Y, AU - Shibata,K, AU - Omura,S, AU - Hino,K, AU - Tomoyasu,S, AU - Tsuruoka,N, PY - 1994/3/1/pubmed PY - 1994/3/1/medline PY - 1994/3/1/entrez SP - 221 EP - 8 JF - Leukemia research JO - Leuk. Res. VL - 18 IS - 3 N2 - The molecular basis of the Philadelphia chromosome (Ph1) is a structurally altered c-abl (bcr/abl) gene which encodes an abnormally large protein with protein tyrosine kinase activity. Herbimycin A, an inhibitor of tyrosine kinase, preferentially inhibited the growth of Ph1-positive acute lymphoid leukemia (ALL) cell lines, as well as Ph1-positive chronic myeloid leukemia (CML) cell lines. Although noncytotoxic concentrations of herbimycin A induced erythroid differentiation of two CML-derived cell lines, K562 and KU812, in a previous study, the differentiation-inducing effect of herbimycin A on Ph1-positive ALL cell lines was less strong. Herbimycin A enhanced some differentiation-associated properties of one Ph1-positive ALL cell line, L2, but the effect of herbimycin A on the other Ph1-positive ALL cell lines was cytotoxic rather than cytostatic (differentiation-inducing). Several derivatives of herbimycin A were synthesized and their effects on the cell proliferation of Ph1-positive CML and ALL cell lines were examined. The sensitivities of the Ph1-positive cell lines to herbimycin A derivatives were different from the data on the rat kidney cell line infected with Rous sarcoma virus (v-src) derived from a previous study, suggesting bcr/abl kinase may differ in sensitivity from other tyrosine kinases. Moreover, the sensitivities of the ALL cell lines were not the same as those of the CML cell lines. These results suggest that a specific inhibitor of bcr/abl kinase could be an effective antileukemic agent against Ph1-positive CML or ALL. SN - 0145-2126 UR - https://www.unboundmedicine.com/medline/citation/8139288/Effects_of_herbimycin_A_and_its_derivatives_on_growth_and_differentiation_of_Ph1_positive_acute_lymphoid_leukemia_cell_lines_ L2 - http://www.diseaseinfosearch.org/result/188 DB - PRIME DP - Unbound Medicine ER -